SHAN3_HUMAN
ID SHAN3_HUMAN Reviewed; 1731 AA.
AC Q9BYB0; D7UT47; Q8TET3;
DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=SH3 and multiple ankyrin repeat domains protein 3;
DE Short=Shank3;
DE AltName: Full=Proline-rich synapse-associated protein 2;
DE Short=ProSAP2;
GN Name=SHANK3; Synonyms=KIAA1650, PROSAP2, PSAP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Uchino S., Waga C., Kohsaka S.;
RT "Novel veriants of human SHANK3 gene.";
RL Submitted (JUN-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 935-1731 (ISOFORMS 1/2).
RX PubMed=11258795; DOI=10.1093/dnares/8.1.1;
RA Hirosawa M., Nagase T., Murahashi Y., Kikuno R., Ohara O.;
RT "Identification of novel transcribed sequences on human chromosome 22 by
RT expressed sequence tag mapping.";
RL DNA Res. 8:1-9(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 962-1731 (ISOFORMS 1/2).
RC TISSUE=Spleen;
RA Ohara O., Nagase T., Kikuno R., Okumura K.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1158 AND SER-1162, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1234 AND SER-1253, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7]
RP ALTERNATIVE SPLICING (ISOFORM 2), AND INVOLVEMENT IN NEUROPSYCHIATRIC
RP DISORDERS.
RX PubMed=24186872; DOI=10.1093/hmg/ddt547;
RA Zhu L., Wang X., Li X.L., Towers A., Cao X., Wang P., Bowman R., Yang H.,
RA Goldstein J., Li Y.J., Jiang Y.H.;
RT "Epigenetic dysregulation of SHANK3 in brain tissues from individuals with
RT autism spectrum disorders.";
RL Hum. Mol. Genet. 23:1563-1578(2014).
RN [8]
RP CHROMOSOMAL TRANSLOCATION WITH APPL2.
RX PubMed=11431708; DOI=10.1086/321293;
RA Bonaglia M.C., Giorda R., Borgatti R., Felisari G., Gagliardi C.,
RA Selicorni A., Zuffardi O.;
RT "Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated
RT with the 22q13.3 deletion syndrome.";
RL Am. J. Hum. Genet. 69:261-268(2001).
RN [9]
RP REVIEW.
RX PubMed=10806096; DOI=10.1242/jcs.113.11.1851;
RA Sheng M., Kim E.;
RT "The Shank family of scaffold proteins.";
RL J. Cell Sci. 113:1851-1856(2000).
RN [10]
RP INTERACTION WITH BAIAP2.
RX PubMed=12504591; DOI=10.1006/mcne.2002.1201;
RA Soltau M., Richter D., Kreienkamp H.-J.;
RT "The insulin receptor substrate IRSp53 links postsynaptic shank1 to the
RT small G-protein cdc42.";
RL Mol. Cell. Neurosci. 21:575-583(2002).
RN [11]
RP INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS.
RX PubMed=22922660; DOI=10.1016/j.ejmg.2012.07.009;
RA Vucurovic K., Landais E., Delahaigue C., Eutrope J., Schneider A.,
RA Leroy C., Kabbaj H., Motte J., Gaillard D., Rolland A.C., Doco-Fenzy M.;
RT "Bipolar affective disorder and early dementia onset in a male patient with
RT SHANK3 deletion.";
RL Eur. J. Med. Genet. 55:625-629(2012).
RN [12]
RP INVOLVEMENT IN PHMDS.
RX PubMed=23758760; DOI=10.1186/2040-2392-4-18;
RA Soorya L., Kolevzon A., Zweifach J., Lim T., Dobry Y., Schwartz L.,
RA Frank Y., Wang A.T., Cai G., Parkhomenko E., Halpern D., Grodberg D.,
RA Angarita B., Willner J.P., Yang A., Canitano R., Chaplin W., Betancur C.,
RA Buxbaum J.D.;
RT "Prospective investigation of autism and genotype-phenotype correlations in
RT 22q13 deletion syndrome and SHANK3 deficiency.";
RL Mol. Autism 4:18-18(2013).
RN [13]
RP INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS.
RX PubMed=24153177; DOI=10.1038/nature12630;
RA Han K., Holder J.L. Jr., Schaaf C.P., Lu H., Chen H., Kang H., Tang J.,
RA Wu Z., Hao S., Cheung S.W., Yu P., Sun H., Breman A.M., Patel A., Lu H.C.,
RA Zoghbi H.Y.;
RT "SHANK3 overexpression causes manic-like behaviour with unique
RT pharmacogenetic properties.";
RL Nature 503:72-77(2013).
RN [14]
RP INVOLVEMENT IN PHMDS, FUNCTION IN SYNAPSE FORMATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=24132240; DOI=10.1038/nature12618;
RA Shcheglovitov A., Shcheglovitova O., Yazawa M., Portmann T., Shu R.,
RA Sebastiano V., Krawisz A., Froehlich W., Bernstein J.A., Hallmayer J.F.,
RA Dolmetsch R.E.;
RT "SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion
RT syndrome patients.";
RL Nature 503:267-271(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-913; THR-1234; SER-1253;
RP SER-1636 AND SER-1638, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP INTERACTION WITH CAMK2A.
RX PubMed=28130356; DOI=10.1523/jneurosci.2068-16.2017;
RA Stephenson J.R., Wang X., Perfitt T.L., Parrish W.P., Shonesy B.C.,
RA Marks C.R., Mortlock D.P., Nakagawa T., Sutcliffe J.S., Colbran R.J.;
RT "Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and
RT Causes ASD-Related Behaviors.";
RL J. Neurosci. 37:2216-2233(2017).
RN [17]
RP VARIANTS ARG-321; LEU-341; SER-970; THR-1173; LEU-1263; VAL-1406; THR-1443;
RP SER-1557 AND THR-1654, AND INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS.
RX PubMed=17999366; DOI=10.1086/522590;
RA Moessner R., Marshall C.R., Sutcliffe J.S., Skaug J., Pinto D., Vincent J.,
RA Zwaigenbaum L., Fernandez B., Roberts W., Szatmari P., Scherer S.W.;
RT "Contribution of SHANK3 mutations to autism spectrum disorder.";
RL Am. J. Hum. Genet. 81:1289-1297(2007).
RN [18]
RP VARIANTS CYS-12; GLY-198; THR-224; CYS-300; GLY-963; VAL-1011; HIS-1231;
RP GLY-1566 AND THR-1654, INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS, AND
RP CHARACTERIZATION OF VARIANTS CYS-12 AND CYS-300.
RX PubMed=17173049; DOI=10.1038/ng1933;
RA Durand C.M., Betancur C., Boeckers T.M., Bockmann J., Chaste P.,
RA Fauchereau F., Nygren G., Rastam M., Gillberg I.C., Anckarsaeter H.,
RA Sponheim E., Goubran-Botros H., Delorme R., Chabane N.,
RA Mouren-Simeoni M.-C., de Mas P., Bieth E., Roge B., Heron D., Burglen L.,
RA Gillberg C., Leboyer M., Bourgeron T.;
RT "Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are
RT associated with autism spectrum disorders.";
RL Nat. Genet. 39:25-27(2007).
RN [19]
RP VARIANT SCZD15 TRP-536, AND VARIANTS THR-245; GLN-493; THR-720; THR-952;
RP VAL-1010; LYS-1298; GLY-1333; VAL-1546 AND THR-1645.
RX PubMed=20385823; DOI=10.1073/pnas.0906232107;
RA Gauthier J., Champagne N., Lafreniere R.G., Xiong L., Spiegelman D.,
RA Brustein E., Lapointe M., Peng H., Cote M., Noreau A., Hamdan F.F.,
RA Addington A.M., Rapoport J.L., Delisi L.E., Krebs M.O., Joober R.,
RA Fathalli F., Mouaffak F., Haghighi A.P., Neri C., Dube M.P., Samuels M.E.,
RA Marineau C., Stone E.A., Awadalla P., Barker P.A., Carbonetto S.,
RA Drapeau P., Rouleau G.A.;
RT "De novo mutations in the gene encoding the synaptic scaffolding protein
RT SHANK3 in patients ascertained for schizophrenia.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:7863-7868(2010).
RN [20]
RP VARIANTS PHMDS ALA-141 AND SER-1452.
RX PubMed=22892527; DOI=10.1038/ejhg.2012.175;
RA Boccuto L., Lauri M., Sarasua S.M., Skinner C.D., Buccella D., Dwivedi A.,
RA Orteschi D., Collins J.S., Zollino M., Visconti P., Dupont B., Tiziano D.,
RA Schroer R.J., Neri G., Stevenson R.E., Gurrieri F., Schwartz C.E.;
RT "Prevalence of SHANK3 variants in patients with different subtypes of
RT autism spectrum disorders.";
RL Eur. J. Hum. Genet. 21:310-316(2013).
CC -!- FUNCTION: Major scaffold postsynaptic density protein which interacts
CC with multiple proteins and complexes to orchestrate the dendritic spine
CC and synapse formation, maturation and maintenance. Interconnects
CC receptors of the postsynaptic membrane including NMDA-type and
CC metabotropic glutamate receptors via complexes with GKAP/PSD-95 and
CC HOMER, respectively, and the actin-based cytoskeleton. Plays a role in
CC the structural and functional organization of the dendritic spine and
CC synaptic junction through the interaction with Arp2/3 and WAVE1 complex
CC as well as the promotion of the F-actin clusters. By way of this
CC control of actin dynamics, participates in the regulation of developing
CC neurons growth cone motility and the NMDA receptor-signaling. Also
CC modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to
CC control the AMPA and metabotropic glutamate receptor-mediated synaptic
CC transmission and plasticity. May be required at an early stage of
CC synapse formation and be inhibited by IGF1 to promote synapse
CC maturation. {ECO:0000269|PubMed:24132240}.
CC -!- SUBUNIT: May homomultimerize via its SAM domain. Interacts with BAIAP2,
CC DBNL and SLC17A7/VGLUT1. Interacts with DLGAP1/GKAP, GRM1/MGLUR1,
CC GRM5/MGLUR5 and LZTS3 C-termini via its PDZ domain. Interacts with
CC ABI1, HOMER1, HOMER2, HOMER3 and CTTN/cortactin SH3 domain. Is part of
CC a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts (via PDZ domain)
CC with the GRIA1 subunit of the AMPA receptor (via PDZ-binding motif).
CC Interacts with WASF1 and CYFIP2; the interactions mediate the
CC association of SHANK3 with the WAVE1 complex. Interacts with ARPC2; the
CC interaction probably mediates the association of SHANK3 with the Arp2/3
CC complex. Interacts (via ANK repeats) with SHARPIN and SPTAN1. Interacts
CC (via PDZ domain) with ARHGAP44 (probably via PDZ-binding motif); the
CC interaction takes place in dendritic spines and promotes GRIA1
CC exocytosis (By similarity). Interacts with CAMK2A (PubMed:28130356).
CC Interacts with DIP2A (By similarity). {ECO:0000250|UniProtKB:Q4ACU6,
CC ECO:0000250|UniProtKB:Q9JLU4, ECO:0000269|PubMed:28130356}.
CC -!- INTERACTION:
CC Q9BYB0; P12814: ACTN1; NbExp=2; IntAct=EBI-1752330, EBI-351710;
CC Q9BYB0; Q14155: ARHGEF7; NbExp=2; IntAct=EBI-1752330, EBI-717515;
CC Q9BYB0; P21333: FLNA; NbExp=2; IntAct=EBI-1752330, EBI-350432;
CC Q9BYB0; P62993: GRB2; NbExp=2; IntAct=EBI-1752330, EBI-401755;
CC Q9BYB0; P07910: HNRNPC; NbExp=2; IntAct=EBI-1752330, EBI-357966;
CC Q9BYB0; O75525: KHDRBS3; NbExp=3; IntAct=EBI-1752330, EBI-722504;
CC Q9BYB0; P16333: NCK1; NbExp=4; IntAct=EBI-1752330, EBI-389883;
CC Q9BYB0; Q99435: NELL2; NbExp=2; IntAct=EBI-1752330, EBI-946274;
CC Q9BYB0; Q9NRD5: PICK1; NbExp=2; IntAct=EBI-1752330, EBI-79165;
CC Q9BYB0; P19174: PLCG1; NbExp=2; IntAct=EBI-1752330, EBI-79387;
CC Q9BYB0; P55036: PSMD4; NbExp=2; IntAct=EBI-1752330, EBI-359318;
CC Q9BYB0; Q8IXJ6: SIRT2; NbExp=2; IntAct=EBI-1752330, EBI-477232;
CC Q9BYB0-1; Q01668: CACNA1D; NbExp=2; IntAct=EBI-20939234, EBI-9207771;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24132240}.
CC Postsynaptic density {ECO:0000269|PubMed:24132240}. Cell projection,
CC dendritic spine {ECO:0000250}. Note=In neuronal cells, extends into the
CC region subjacent to the postsynaptic density (PSD). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Comment=Additional isoforms seem to exist. These isoforms may be the
CC product of multiple intragenic promoter and/or alternative splicing.;
CC Name=1; Synonyms=A;
CC IsoId=Q9BYB0-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=Q9BYB0-3; Sequence=VSP_053605;
CC -!- TISSUE SPECIFICITY: Expressed in the cerebral cortex and the
CC cerebellum.
CC -!- DOMAIN: In isoform 1, the N-terminal region preceding the ANK repeats
CC interacts with the 6 ANK repeats in an intramolecular manner, thereby
CC restricting access to ligands, such as SHARPIN and SPTAN1.
CC {ECO:0000250}.
CC -!- DISEASE: Note=A chromosomal aberration involving SHANK3 is found in
CC patients with chromosome 22q13.3 deletion syndrome. Translocation
CC t(12;22)(q24.1;q13.3) with APPL2/DIP13B. {ECO:0000269|PubMed:11431708}.
CC -!- DISEASE: Note=Defects in SHANK3 are associated with neuropsychiatric
CC disorders such as autism spectrum disorders (ASD), bipolar affective
CC disorders and early dementia onset. ASD are characterized by
CC impairments in reciprocal social interaction and communication as well
CC as restricted and stereotyped patterns of interest and activities. ASD
CC include forms with moderate to severe cognitive impairment and milder
CC forms with higher cognitive ability (Asperger syndrome). Gene
CC duplication is associated with hyperkinetic neuropsychiatric disorders
CC (PubMed:24153177) such as hyperactivity, auditory overstimulation,
CC epilepsy and bipolar affective disorders, among others.
CC {ECO:0000269|PubMed:24153177}.
CC -!- DISEASE: Phelan-McDermid syndrome (PHMDS) [MIM:606232]: A developmental
CC disorder with variable features. Common features include neonatal
CC hypotonia, global developmental delay, normal to accelerated growth,
CC absent to severely delayed speech, autistic behavior, and minor
CC dysmorphic features. {ECO:0000269|PubMed:22892527,
CC ECO:0000269|PubMed:23758760, ECO:0000269|PubMed:24132240}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Schizophrenia 15 (SCZD15) [MIM:613950]: A complex,
CC multifactorial psychotic disorder or group of disorders characterized
CC by disturbances in the form and content of thought (e.g. delusions,
CC hallucinations), in mood (e.g. inappropriate affect), in sense of self
CC and relationship to the external world (e.g. loss of ego boundaries,
CC withdrawal), and in behavior (e.g bizarre or apparently purposeless
CC behavior). Although it affects emotions, it is distinguished from mood
CC disorders in which such disturbances are primary. Similarly, there may
CC be mild impairment of cognitive function, and it is distinguished from
CC the dementias in which disturbed cognitive function is considered
CC primary. Some patients manifest schizophrenic as well as bipolar
CC disorder symptoms and are often given the diagnosis of schizoaffective
CC disorder. {ECO:0000269|PubMed:20385823}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 1]: Primarily expressed in neurons.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative promoter usage.
CC {ECO:0000305}.
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DR EMBL; AC000050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC000036; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB051437; BAB33320.1; -; mRNA.
DR EMBL; AK074038; BAB84864.1; -; mRNA.
DR EMBL; AB569469; BAJ09793.1; -; mRNA.
DR RefSeq; NP_277052.1; NM_033517.1.
DR PDB; 6CPK; NMR; -; A=471-530.
DR PDB; 7C7I; X-ray; 2.28 A; C/D=1-99.
DR PDB; 7C7J; X-ray; 2.39 A; C/D=1-99.
DR PDBsum; 6CPK; -.
DR PDBsum; 7C7I; -.
DR PDBsum; 7C7J; -.
DR AlphaFoldDB; Q9BYB0; -.
DR SMR; Q9BYB0; -.
DR BioGRID; 124487; 170.
DR CORUM; Q9BYB0; -.
DR DIP; DIP-52267N; -.
DR IntAct; Q9BYB0; 192.
DR MINT; Q9BYB0; -.
DR TCDB; 8.A.28.1.7; the ankyrin (ankyrin) family.
DR CarbonylDB; Q9BYB0; -.
DR iPTMnet; Q9BYB0; -.
DR PhosphoSitePlus; Q9BYB0; -.
DR BioMuta; SHANK3; -.
DR DMDM; 148887434; -.
DR jPOST; Q9BYB0; -.
DR MassIVE; Q9BYB0; -.
DR PaxDb; Q9BYB0; -.
DR PeptideAtlas; Q9BYB0; -.
DR PRIDE; Q9BYB0; -.
DR ProteomicsDB; 79606; -. [Q9BYB0-1]
DR ABCD; Q9BYB0; 2 sequenced antibodies.
DR GeneCards; SHANK3; -.
DR GeneReviews; SHANK3; -.
DR HGNC; HGNC:14294; SHANK3.
DR MalaCards; SHANK3; -.
DR MIM; 606230; gene.
DR MIM; 606232; phenotype.
DR MIM; 613950; phenotype.
DR neXtProt; NX_Q9BYB0; -.
DR Orphanet; 48652; Monosomy 22q13.3.
DR Orphanet; 106; NON RARE IN EUROPE: Autism.
DR InParanoid; Q9BYB0; -.
DR OrthoDB; 98033at2759; -.
DR PathwayCommons; Q9BYB0; -.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; Q9BYB0; -.
DR SIGNOR; Q9BYB0; -.
DR BioGRID-ORCS; 85358; 11 hits in 252 CRISPR screens.
DR ChiTaRS; SHANK3; human.
DR GeneWiki; SHANK3; -.
DR GenomeRNAi; 85358; -.
DR Pharos; Q9BYB0; Tbio.
DR PRO; PR:Q9BYB0; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q9BYB0; protein.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0060170; C:ciliary membrane; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0043005; C:neuron projection; ISS:BHF-UCL.
DR GO; GO:0044309; C:neuron spine; ISS:BHF-UCL.
DR GO; GO:0014069; C:postsynaptic density; ISS:BHF-UCL.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISS:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; ISS:BHF-UCL.
DR GO; GO:0043621; F:protein self-association; ISS:BHF-UCL.
DR GO; GO:0097110; F:scaffold protein binding; ISS:BHF-UCL.
DR GO; GO:0017124; F:SH3 domain binding; ISS:BHF-UCL.
DR GO; GO:0030160; F:synaptic receptor adaptor activity; ISS:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; ISS:BHF-UCL.
DR GO; GO:0030534; P:adult behavior; IMP:BHF-UCL.
DR GO; GO:0097113; P:AMPA glutamate receptor clustering; ISS:BHF-UCL.
DR GO; GO:0048854; P:brain morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:BHF-UCL.
DR GO; GO:0097117; P:guanylate kinase-associated protein clustering; ISS:BHF-UCL.
DR GO; GO:0007612; P:learning; IMP:BHF-UCL.
DR GO; GO:0000165; P:MAPK cascade; ISS:BHF-UCL.
DR GO; GO:0007613; P:memory; ISS:BHF-UCL.
DR GO; GO:0032232; P:negative regulation of actin filament bundle assembly; ISS:BHF-UCL.
DR GO; GO:0045794; P:negative regulation of cell volume; ISS:BHF-UCL.
DR GO; GO:0097114; P:NMDA glutamate receptor clustering; ISS:BHF-UCL.
DR GO; GO:2000969; P:positive regulation of AMPA receptor activity; ISS:BHF-UCL.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISS:BHF-UCL.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:BHF-UCL.
DR GO; GO:1900451; P:positive regulation of glutamate receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; ISS:BHF-UCL.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISS:BHF-UCL.
DR GO; GO:0051835; P:positive regulation of synapse structural plasticity; ISS:BHF-UCL.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:BHF-UCL.
DR GO; GO:0097107; P:postsynaptic density assembly; ISS:BHF-UCL.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:BHF-UCL.
DR GO; GO:1900452; P:regulation of long-term synaptic depression; ISS:BHF-UCL.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISS:BHF-UCL.
DR GO; GO:0035176; P:social behavior; IMP:BHF-UCL.
DR GO; GO:0021773; P:striatal medium spiny neuron differentiation; ISS:BHF-UCL.
DR GO; GO:0007416; P:synapse assembly; ISS:BHF-UCL.
DR GO; GO:0042297; P:vocal learning; IMP:BHF-UCL.
DR GO; GO:0071625; P:vocalization behavior; IMP:BHF-UCL.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 1.25.40.20; -; 2.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF17820; PDZ_6; 1.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF07653; SH3_2; 1.
DR SMART; SM00248; ANK; 5.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative promoter usage; ANK repeat;
KW Autism spectrum disorder; Cell projection; Chromosomal rearrangement;
KW Coiled coil; Cytoplasm; Disease variant; Methylation; Phosphoprotein;
KW Reference proteome; Repeat; Schizophrenia; SH3 domain; SH3-binding;
KW Synapse.
FT CHAIN 1..1731
FT /note="SH3 and multiple ankyrin repeat domains protein 3"
FT /id="PRO_0000174675"
FT REPEAT 148..178
FT /note="ANK 1"
FT REPEAT 182..211
FT /note="ANK 2"
FT REPEAT 215..245
FT /note="ANK 3"
FT REPEAT 249..278
FT /note="ANK 4"
FT REPEAT 282..311
FT /note="ANK 5"
FT REPEAT 315..345
FT /note="ANK 6"
FT DOMAIN 471..530
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 571..665
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1668..1731
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..75
FT /note="Intramolecular interaction with the ANK repeats"
FT /evidence="ECO:0000250"
FT REGION 407..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 665..689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 678..685
FT /note="Required for interaction with ABI1"
FT /evidence="ECO:0000250"
FT REGION 760..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 871..1021
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1115..1460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1475..1525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1546..1584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1627..1664
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1494..1514
FT /evidence="ECO:0000255"
FT MOTIF 1410..1416
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 439..465
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 779..793
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 810..847
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1175..1193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1327..1348
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1367..1400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1495..1509
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1638..1658
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 122
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLU4"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 556
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 791
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 802
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 891
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 898
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 913
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 931
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLU4"
FT MOD_RES 966
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1129
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1158
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT MOD_RES 1162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT MOD_RES 1165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1234
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1253
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1420
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLU4"
FT MOD_RES 1510
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1529
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1539
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1634
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1636
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1638
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..119
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053605"
FT VARIANT 12
FT /note="R -> C (found in patients with neuropsychiatric
FT disorders; unknown pathological significance; disrupts
FT synaptic localization; dbSNP:rs1336089966)"
FT /evidence="ECO:0000269|PubMed:17173049"
FT /id="VAR_032804"
FT VARIANT 141
FT /note="P -> A (in PHMDS; dbSNP:rs397514705)"
FT /evidence="ECO:0000269|PubMed:22892527"
FT /id="VAR_070259"
FT VARIANT 198
FT /note="A -> G (in dbSNP:rs1232069989)"
FT /evidence="ECO:0000269|PubMed:17173049"
FT /id="VAR_032805"
FT VARIANT 224
FT /note="A -> T (in dbSNP:rs766856815)"
FT /evidence="ECO:0000269|PubMed:17173049"
FT /id="VAR_032806"
FT VARIANT 245
FT /note="I -> T (in dbSNP:rs9616915)"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_032807"
FT VARIANT 300
FT /note="R -> C (found in patients with neuropsychiatric
FT disorders; unknown pathological significance; disrupts
FT synaptic localization; dbSNP:rs376862893)"
FT /evidence="ECO:0000269|PubMed:17173049"
FT /id="VAR_032808"
FT VARIANT 321
FT /note="Q -> R (found in a patient with neuropsychiatric
FT disorders; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:17999366"
FT /id="VAR_070260"
FT VARIANT 341
FT /note="S -> L (found in patient with neuropsychiatric
FT disorders; unknown pathological significance;
FT dbSNP:rs1314696433)"
FT /evidence="ECO:0000269|PubMed:17999366"
FT /id="VAR_070261"
FT VARIANT 493
FT /note="H -> Q"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065799"
FT VARIANT 536
FT /note="R -> W (in SCZD15; dbSNP:rs387906933)"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065800"
FT VARIANT 720
FT /note="A -> T"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065801"
FT VARIANT 952
FT /note="S -> T (in dbSNP:rs1340094921)"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065802"
FT VARIANT 963
FT /note="A -> G"
FT /evidence="ECO:0000269|PubMed:17173049"
FT /id="VAR_070262"
FT VARIANT 970
FT /note="A -> S (found in a patient with neuropsychiatric
FT disorders; unknown pathological significance;
FT dbSNP:rs530255181)"
FT /evidence="ECO:0000269|PubMed:17999366"
FT /id="VAR_070263"
FT VARIANT 1010
FT /note="G -> V"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065803"
FT VARIANT 1011
FT /note="G -> V (in dbSNP:rs767058690)"
FT /evidence="ECO:0000269|PubMed:17173049"
FT /id="VAR_070264"
FT VARIANT 1134
FT /note="P -> H (in dbSNP:rs769454362)"
FT /id="VAR_065804"
FT VARIANT 1173
FT /note="A -> T (found in a patient with neuropsychiatric
FT disorders; unknown pathological significance;
FT dbSNP:rs139686326)"
FT /evidence="ECO:0000269|PubMed:17999366"
FT /id="VAR_070265"
FT VARIANT 1231
FT /note="R -> H (in dbSNP:rs750186589)"
FT /evidence="ECO:0000269|PubMed:17173049"
FT /id="VAR_070266"
FT VARIANT 1263
FT /note="P -> L (found in a patient with neuropsychiatric
FT disorders; unknown pathological significance;
FT dbSNP:rs757572910)"
FT /evidence="ECO:0000269|PubMed:17999366"
FT /id="VAR_070267"
FT VARIANT 1298
FT /note="R -> K (in dbSNP:rs201483867)"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065805"
FT VARIANT 1333
FT /note="V -> G (in dbSNP:rs200087210)"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065806"
FT VARIANT 1406
FT /note="L -> V (found in a patient with neuropsychiatric
FT disorders; unknown pathological significance;
FT dbSNP:rs201973139)"
FT /evidence="ECO:0000269|PubMed:17999366"
FT /id="VAR_070268"
FT VARIANT 1443
FT /note="M -> T (found in a patient with neuropsychiatric
FT disorders; unknown pathological significance;
FT dbSNP:rs773395828)"
FT /evidence="ECO:0000269|PubMed:17999366"
FT /id="VAR_070269"
FT VARIANT 1452
FT /note="A -> S (in PHMDS)"
FT /evidence="ECO:0000269|PubMed:22892527"
FT /id="VAR_070270"
FT VARIANT 1546
FT /note="I -> V (in dbSNP:rs1389307970)"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065807"
FT VARIANT 1557
FT /note="G -> S (found in a patient with neuropsychiatric
FT disorders; unknown pathological significance;
FT dbSNP:rs1224063430)"
FT /evidence="ECO:0000269|PubMed:17999366"
FT /id="VAR_070271"
FT VARIANT 1566
FT /note="S -> G (in dbSNP:rs1481014682)"
FT /evidence="ECO:0000269|PubMed:17173049"
FT /id="VAR_070272"
FT VARIANT 1645
FT /note="P -> T"
FT /evidence="ECO:0000269|PubMed:20385823"
FT /id="VAR_065808"
FT VARIANT 1654
FT /note="P -> T (found in patients with neuropsychiatric
FT disorders; unknown pathological significance;
FT dbSNP:rs749130556)"
FT /evidence="ECO:0000269|PubMed:17173049,
FT ECO:0000269|PubMed:17999366"
FT /id="VAR_070273"
FT STRAND 9..15
FT /evidence="ECO:0007829|PDB:7C7I"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:7C7I"
FT STRAND 20..26
FT /evidence="ECO:0007829|PDB:7C7I"
FT HELIX 32..42
FT /evidence="ECO:0007829|PDB:7C7I"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:7C7I"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:7C7I"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:7C7I"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:7C7J"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:7C7I"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:7C7I"
FT STRAND 87..92
FT /evidence="ECO:0007829|PDB:7C7I"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:6CPK"
FT STRAND 486..489
FT /evidence="ECO:0007829|PDB:6CPK"
FT STRAND 497..503
FT /evidence="ECO:0007829|PDB:6CPK"
FT STRAND 505..513
FT /evidence="ECO:0007829|PDB:6CPK"
FT STRAND 516..521
FT /evidence="ECO:0007829|PDB:6CPK"
FT HELIX 522..524
FT /evidence="ECO:0007829|PDB:6CPK"
FT STRAND 525..527
FT /evidence="ECO:0007829|PDB:6CPK"
SQ SEQUENCE 1731 AA; 184667 MW; 781936CE60988D08 CRC64;
MDGPGASAVV VRVGIPDLQQ TKCLRLDPAA PVWAAKQRVL CALNHSLQDA LNYGLFQPPS
RGRAGKFLDE ERLLQEYPPN LDTPLPYLEF RYKRRVYAQN LIDDKQFAKL HTKANLKKFM
DYVQLHSTDK VARLLDKGLD PNFHDPDSGE CPLSLAAQLD NATDLLKVLK NGGAHLDFRT
RDGLTAVHCA TRQRNAAALT TLLDLGASPD YKDSRGLTPL YHSALGGGDA LCCELLLHDH
AQLGITDENG WQEIHQACRF GHVQHLEHLL FYGADMGAQN ASGNTALHIC ALYNQESCAR
VLLFRGANRD VRNYNSQTAF QVAIIAGNFE LAEVIKTHKD SDVVPFRETP SYAKRRRLAG
PSGLASPRPL QRSASDINLK GEAQPAASPG PSLRSLPHQL LLQRLQEEKD RDRDADQESN
ISGPLAGRAG QSKISPSGPG GPGPAPGPGP APPAPPAPPP RGPKRKLYSA VPGRKFIAVK
AHSPQGEGEI PLHRGEAVKV LSIGEGGFWE GTVKGRTGWF PADCVEEVQM RQHDTRPETR
EDRTKRLFRH YTVGSYDSLT SHSDYVIDDK VAVLQKRDHE GFGFVLRGAK AETPIEEFTP
TPAFPALQYL ESVDVEGVAW RAGLRTGDFL IEVNGVNVVK VGHKQVVALI RQGGNRLVMK
VVSVTRKPEE DGARRRAPPP PKRAPSTTLT LRSKSMTAEL EELASIRRRK GEKLDEMLAA
AAEPTLRPDI ADADSRAATV KQRPTSRRIT PAEISSLFER QGLPGPEKLP GSLRKGIPRT
KSVGEDEKLA SLLEGRFPRS TSMQDPVREG RGIPPPPQTA PPPPPAPYYF DSGPPPAFSP
PPPPGRAYDT VRSSFKPGLE ARLGAGAAGL YEPGAALGPL PYPERQKRAR SMIILQDSAP
ESGDAPRPPP AATPPERPKR RPRPPGPDSP YANLGAFSAS LFAPSKPQRR KSPLVKQLQV
EDAQERAALA VGSPGPGGGS FAREPSPTHR GPRPGGLDYG AGDGPGLAFG GPGPAKDRRL
EERRRSTVFL SVGAIEGSAP GADLPSLQPS RSIDERLLGT GPTAGRDLLL PSPVSALKPL
VSGPSLGPSG STFIHPLTGK PLDPSSPLAL ALAARERALA SQAPSRSPTP VHSPDADRPG
PLFVDVQARD PERGSLASPA FSPRSPAWIP VPARREAEKV PREERKSPED KKSMILSVLD
TSLQRPAGLI VVHATSNGQE PSRLGGAEEE RPGTPELAPA PMQSAAVAEP LPSPRAQPPG
GTPADAGPGQ GSSEEEPELV FAVNLPPAQL SSSDEETREE LARIGLVPPP EEFANGVLLA
TPLAGPGPSP TTVPSPASGK PSSEPPPAPE SAADSGVEEA DTRSSSDPHL ETTSTISTVS
SMSTLSSESG ELTDTHTSFA DGHTFLLEKP PVPPKPKLKS PLGKGPVTFR DPLLKQSSDS
ELMAQQHHAA SAGLASAAGP ARPRYLFQRR SKLWGDPVES RGLPGPEDDK PTVISELSSR
LQQLNKDTRS LGEEPVGGLG SLLDPAKKSP IAAARLFSSL GELSSISAQR SPGGPGGGAS
YSVRPSGRYP VARRAPSPVK PASLERVEGL GAGAGGAGRP FGLTPPTILK SSSLSIPHEP
KEVRFVVRSV SARSRSPSPS PLPSPASGPG PGAPGPRRPF QQKPLQLWSK FDVGDWLESI
HLGEHRDRFE DHEIEGAHLP ALTKDDFVEL GVTRVGHRMN IERALRQLDG S
